Tumors of the CNS affect children and predominantly the younger adult age group, often with devastating consequences. The CNS is a 'sanctuary' site which may allow malignant cells to escape immune surveillance. Dendritic cells, the skilled antigen presenting cells, vastly improve the antigen recognition ability of the neuroimmune system and play a critical role in immune surveillance even in 'sanctuary' sites such as the CNS. We have developed a cell culture system for dendritic cell isolation and growth. In this proposal we will further develop the culture system and carefully characterize these cells for phenotypic, morphological and functional characteristics. Skillful utilization of such optimally functional dendritic cells can bring the hitherto 'underprivileged' CNS under surveillance and lead to a better understanding of the comprehensive immune defence against tumors and other antigens. The valuable and meaningful insights gained from these experiments can serve as an effective paradigm to device effective immunotherapeutic interventions to treat a variety of neuroimmune diseases and infections of the CNS. PROPOSED COMMERCIAL APPLICATION: Malignancy affects a third of the population at some time in their life, often with devastating economic consequences. Failure of immune surveillance may allow neoplastic cells to establish themselves and proliferate, especially in 'sanctuary' sites such as the CNS, resulting in clinical malignancy. Dendritic cells can be developed as a highly potent, relatively non-toxic therapy for malignancies, infectious and immune diseases of the CNS.